EVIDENCE FOR IMMUNE SELECTION OF HEPATITIS-C VIRUS (HCV) PUTATIVE ENVELOPE GLYCOPROTEIN VARIANTS - POTENTIAL ROLE IN CHRONIC HCV INFECTIONS
EVIDENCE FOR IMMUNE SELECTION OF HEPATITIS-C VIRUS (HCV) PUTATIVE ENVELOPE GLYCOPROTEIN VARIANTS - POTENTIAL ROLE IN CHRONIC HCV INFECTIONS
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DOI：
10.1073/pnas.89.8.3468
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发表时间：
1992-04-15
影响因子：
11.1
通讯作者：
HOUGHTON, M
中科院分区：
文献类型：
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作者：
WEINER, AJ;GEYSEN, HM;HOUGHTON, M
E2/非结构蛋白1是HCV推定的包膜糖蛋白（gp 72），具有N末端高变（E2 HV）结构域，其氨基酸384至414的意义未知。E2 HV结构域中的高度氨基酸序列变异似乎与在人免疫缺陷病毒1型gp 120 V3结构域中观察到的高度氨基酸序列变异相当。这一观察结果以及HCV E2 HV结构域缺乏保守二级结构的观察结果意味着，与人免疫缺陷病毒1 gp 120的V3环一样，N-末端E2区可能编码受免疫选择的保护性表位。抗体-表位结合研究揭示了位于E2 HV区域的5个分离物特异性线性表位。这些结果表明，E2 HV结构域是人类免疫应答的靶点，并且除了由HCV分离株之间的核苷酸和氨基酸序列同一性定义的HCV的三个主要组之外，还存在E2 HV特异性亚组。对两个人的部分或完整E2序列的分析表明，E2 HV变体可以同时共存于单个个体中，或者特定变体可能在不同的疾病发作期间占主导地位。在后一种情况下，我们发现一个人谁开发抗体的E2 HV域（氨基酸396-407）的一个亚区，具体到一个变异，主要是在一个重大的肝炎发作，但缺乏可检测的抗体的相应区域的第二个变异，主要是在以后的疾病发作。这些数据表明，E2 HV结构域的变异性可能是由免疫选择引起的。本报告的发现可能会影响旨在控制和消除HCV的疫苗策略和药物治疗计划。
E2/nonstructural protein 1, the putative envelope glycoprotein (gp72) of HCV, possesses an N-terminal hypervariable (E2 HV) domain from amino acids 384 to 414 of unknown significance. The high degree of amino acid sequence variation in the E2 HV domain appears to be comparable to that,observed in the human immunodeficiency virus type 1 gp120 V3 domain. This observation and the observation that the HCV E2 HV domain lacks conserved secondary structure imply that, like the V3 loop of human immunodeficiency virus 1 gp120, the N-terminal E2 region may encode protective epitopes that are subject to immune selection. Antibody-epitope binding studies revealed five isolate-specific linear epitopes located in the E2 HV region. These results suggest that the E2 HV domain is a target for the human immune response and that, in addition to the three major groups of HCV, defined by nucleotide and amino acid sequence identity among HCV isolates, E2 HV-specific subgroups also exist. Analysis of the partial or complete E2 sequences of two individuals indicated that E2 HV variants can either coexist simultaneously in a single individual or that a particular variant may predominate during different episodes of disease. In the latter situation, we found one individual who developed antibodies to a subregion of the E2 HV domain (amino acids 396-407) specific to a variant that was predominant during one major episode of hepatitis but who lacked detectable antibodies to the corresponding region of a second variant that was predominant during a later episode of disease. The data suggest that the variability in the E2 HV domain may result from immune selection. The findings of this report could impact vaccine strategies and drug therapy programs designed to control and eliminate HCV.